Acot4, an isoform of the acyl-CoA thioesterase (ACOT) family, catalyzes the hydrolysis of acyl-CoA thioesters to non-esterified fatty acid and coenzyme A (CoA) [1,3,5,7]. It is involved in lipid metabolism pathways and has been shown to be important in maintaining normal cellular lipid homeostasis [1,2,4,6,7]. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, can be valuable in further exploring its functions.

Depletion of Acot4 attenuated the proliferation and tumour formation of pancreatic ductal carcinoma (PDAC) cells, and its expression in PDAC was negatively correlated with patient survival, indicating its role in pancreatic tumourigenesis [1]. In hepatocytes, Acot4 knockdown alleviated gluconeogenesis and lipid accumulation, suggesting its relation to hepatic glucose and lipid metabolism, potentially via regulation of AMP-activated protein kinase (AMPK) activity [2]. In early-weaned rats, Acot4 expression was influenced by early weaning, which disrupted lipid metabolism, and leucine supplementation that alleviated metabolic disorders may have affected Acot4-related lipid metabolic processes [4].

In conclusion, Acot4 plays essential roles in lipid metabolism, including in tumourigenesis, hepatic metabolism, and early-life programming of obesity. The study of Acot4 using KO or CKO mouse models has provided insights into its functions in these disease-related areas, helping to understand the underlying mechanisms and potentially offering new directions for treatment and prevention.